Efficiency and safety of single anastomosis sleeve ileal (SASI) bypass in the treatment of obesity and associated comorbidities: a systematic review and meta-analysis

Introduction The Single Anastomosis Sleeve Ileal (SASI) bypass is a new bariatric surgery corresponding to an adaptation of the Santoro approach, consisting of a sleeve gastrectomy (SG) followed by loop gastroileostomy. Therefore, we aimed to systematically assess all the current literature on SASI bypass in terms of safety, weight loss, improvement in associated comorbidities, and complications. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) recommendations, we conducted a systematic review and meta-analysis by searching three databases (PubMed, Scopus, and Web of Science). We performed a meta-analysis of risk ratios and mean differences to compare surgical approaches for excessive weight loss, improvement/remission in type 2 diabetes mellitus (T2DM), hypertension (HT), dyslipidemia (DL), obstructive sleep apnea (OSA), and complications. Heterogeneity was assessed using the I2 statistic. Results Eighteen studies were included in the qualitative analysis and four in the quantitative analysis, comparing SASI bypass with SG and One-Anastomosis Gastric Bypass (OAGB). A comparison between Roux-en-Y Gastric Bypass (RYGB) and SASI bypass could not be performed. Compared to SG, the SASI bypass was associated with improved weight loss (MD = 11.32; 95% confidence interval (95%CI) [7.89;14.76]; p < 0.0001), and improvement or remission in T2DM (RR = 1.35; 95%CI [1.07;1.69]; p = 0.011), DL (RR = 1.41; 95%CI [1.00;1.99]; p = 0.048) and OSA (RR = 1.50; 95%CI [1.01;2.22]; p = 0.042). No statistically significant differences in any of the assessed outcomes were observed when compared with OAGB. When compared to both SG and OAGB, the complication rate of SASI was similar. Conclusion Although studies with longer follow-up periods are needed, this systematic review and meta-analysis showed that SASI bypass has a significant effect on weight loss and metabolic variables. Variations in outcomes between studies reinforce the need for standardization. Supplementary Information The online version contains supplementary material available at 10.1007/s00423-024-03413-w.


Introduction
With the growing prevalence of obesity, it has become a major public health concern [1].Conservative treatment typically fails to provide satisfactory results.However, bariatric surgery has proven to be the most effective treatment [2].
The most common procedure is the Sleeve Gastrectomy (SG) followed by Roux-en-Y Gastric Bypass (RYGB) [3].
In 2014, Mui et al. described a new technique that was adapted from the Santoro approach, which consisted of SG followed by loop gastroileostomy 250 cm proximal of the ileocecal valve [4].In 2016, Mahdy et al. presented the first case series of 50 patients with 1-year follow-up and named it the Single Anastomosis Sleeve Ileal (SASI) bypass [5].By changing the Roux-en-Y anastomosis of Santoro to a simple loop, the SASI bypass appears to be a simpler and safer technique without losing benefits in the treatment of obesity and its comorbidities.
Several studies evaluated the efficacy and safety of this technique.The common limb length varied between 200 and 350 cm.Due to this variation, some authors referred to this technique as "Laparoscopic sleeve gastrectomy with loop bipartition" [6,7], "Laparoscopic sleeve gastrectomy with loop gastroileal bypass" [8] and "Laparoscopic sleeve gastrectomy with transit loop bipartition" [9].
Therefore, we aimed to systematically assess the current literature on SASI bypass in terms of safety, weight loss, improvement in associated comorbidities, and complications.Additionally, we aimed to establish a comparison with other bariatric surgeries.To the best of our knowledge, this is the first meta-analysis comparing this technique with other bariatric procedures.This study will contribute to a better understanding of this technique and will allow standardization for improved outcomes in the future.

Methods
This systematic review and meta-analysis was conducted by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines [10].

Eligibility of primary studies
We included studies assessing adult patients with obesity who underwent SASI bypass.We included both single-arm studies and experimental or observational studies comparing SASI bypass with other bariatric surgeries.
We excluded animal studies, unrelated articles, editorials, correspondence, video reports, reviews, and meta-analyses.In addition, we excluded studies assessing less than 10 participants.

Search strategy
In October 2022, a systematic review of the available literature was conducted using three search databases -PubMed, Scopus, and Web of Science.The search queries are listed in Supplementary Table 1.In addition, reference lists of the primary articles were hand-searched.
We considered only studies published after 2013, as this technique was first described in 2014 by Mui et al. [4].

Study selection
After removing the duplicates, study selection was conducted independently by two authors (C.O. and M.O.) in two separate phases.Firstly, the articles were searched by title and abstract.Subsequently, articles not excluded were selected based on their full-text reading.Any disagreements were discussed between the reviewers and a third author (H.S.S.).

Data collection process
Data were independently extracted by two authors (C.O. and M.O.) into a predesigned data extraction form that was developed according to the Cochrane Handbook [11] to extract relevant information such as author name, publication year, country and journal of the publication, study design, duration of follow-up, sample size, PICO, patient inclusion and exclusion criteria, participants characteristics (mean age, percentage of each gender, mean BMI, number of patients with T2DM, HT, DL, GERD and OSA), interventions, specifics measures of the SASI bypass, outcomes measures (weight loss and improvement in comorbidities), and every kind of complications after surgery.

Quality assessment
The quality of the studies was independently assessed by two reviewers (M.C. and C.O.) using the National Institutes of Health quality assessment criteria for Observational studies [12], and the Cochrane Collaboration Risk of Bias Tool for randomized control trials (RCT) [13].
The first tool is 14 questions of yes or no, resulting in a final rating (Good, Fair, or Poor).Because exposure is a surgical procedure that can't be quantified or measured more than once, questions assessing these parameters were considered not applicable.
The second tool classifies each study as having a high, low, or unclear risk bias, based on selection, performance, detection, elimination, reporting, and other bias factors.

Quantitative synthesis of results
We performed a random-effects meta-analysis (using the restricted maximum likelihood approach) of mean differences (MD) for the continuous outcome (percentage of excess weight loss, %EWL) and relative risks (RR) for dichotomous variables (improvement or remission of T2DM, HT, DL, OSA, and complications).
Heterogeneity was evaluated using Cochran's Q statistic p-value and the I 2 statistic.Heterogeneity was considered high if I 2 > 50% or Cochran's Q test p-value < 0.10.Sources of heterogeneity were studied using leave-one-out sensitivity analysis.
A p-value lower than 0.05 was considered statistically significant.The meta package of software R was used to analyse the data for the meta-analysis.
%EWL is a measured that is calculated as [(preoperative weight-weight on follow-up)/ (preoperative weight -ideal weight)] x 100, with an ideal weight corresponding to an BMI of 25 kg/m 2 .

Study selection
After the search in the databases, a total of 840 studies were found, of which 409 were duplicates.After the screening phase, 15 articles were fully read, and all were included.Hand searching resulted in 3 additional articles.A total of 18 articles were included in the qualitative synthesis and 4 in the quantitative synthesis.The study selection process is summarized in Fig. 1 [10].

Risk of bias of individual studies
The risk of bias in the observational studies is demonstrated in the Supplementary Table 2. Most studies failed to justify the sample size, and none ensured that the assessors were blinded to the exposure status.Only two studies had a loss of follow-up after baseline higher than 20%.For the other criteria, most studies showed a low risk of bias.Therefore, all studies were considered good or fair.
The results of the quality assessment of RCT are shown in Supplementary Table 3 [27].Overall, this study was considered to have a low risk of bias since only two parameters were considered unclear.
Five studies made a comparison with SG (3 retrospective, 1 prospective, 1 RCT) and 2 retrospective studies made a comparison with OAGB (Table 1).
A total of 1714 patients were studied, with sample sizes ranging from 19 to 551.The follow-up time ranged between 3 months and 36 months.a -NIH (National Institutes of Health) quality assessment criteria for observational studies: it is based on a quality rating of G (good), F (fair), and P (poor), and 14 questions that can be answered with yes/no/not applicable/not reported/cannot determine.Y/N is the ratio of questions with positive answers (Y-yes) and negative answers (N-no) *Common channel length was 250 cm in 18 patients, 300 cm in 88 patients, and 350 cm in 7 patients **The length of the CL was determined according to the total bowel length (TBL).If the TBL was ≤ 6 m, the CL length was 250 cm.The CL length was 300 cm if the TBL was more than 6 m. 250 cm was performed 36% (116) of the time and 300 cm 64% of the time (206)

Comparison between SASI bypass and OAGB
In the comparison between SASI bypass and OAGB, it was not possible to establish a comparison regarding weight loss due to the lack of data.

Percentage of excess weight loss
A total of 329 patients were analysed in three studies on %EWL after 12 months (Fig. 2a).SASI was found to be significantly better than SG in the meta-analytical %EWD MD (MD = 11.32;95%CI[7.89;14.76];p < 0.0001), with a moderate heterogeneity (I 2 = 11%; p = 0.33).Heterogeneity ceased to be observed after removing the study by Madyan et al. (Supplementary Table 4).

Type 2 diabetes mellitus
A total of 124 patients were analysed in four studies that compared SASI versus SG on the partial or complete remission of T2DM after 12 months.

Hypertension
Four studies compared SASI and SG on the improvement or resolution of HT in these two techniques (101 patients) after 12 months.The results presented in Fig. 2c show no significant difference (RR = 1.10; 95%CI[0.82;1.46];p = 0.532) between the two approaches, and no heterogeneity was detected (I 2 = 0%; p = 0.95).

Dyslipidemia
A total of 68 patients were analysed in two studies that compared partial or complete remission of DL after 12 months.

Obstructive sleep apnea
A total of 34 patients were analysed in two studies that compared partial or complete remission of OSA after 12 months.

Summary of evidence
The ideal bariatric surgery should be safe, technically simple, and successful in reducing weight and treating comorbidities [29].The Santoro technique [30] was the foundation for SASI bypass, which had the goals of facilitating the procedure and try to lower the risk of complications, by reducing the number of anastomoses [5].
Owing to the limited sample size and lack of research, we were unable to establish a comparison for the meta-analysis of this outcome.
Two studies reported results regarding complete remission of non-alcoholic fatty liver disease (NAFLD) after 12 months.Kermansanavi et al. reported a rate of approximately 73% [22], and Hosseini et al. reported a rate of 90% [14].Although these results are promising, further studies are needed to evaluate the efficiency of SASI bypass in NAFLD remission.In both studies, abdominal ultrasonography was performed to assess improvement in NAFLD.
Regarding the occurrence of biliary reflux, only one article reported a patient with evidence of severe biliary reflux on upper endoscopy, and he was managed by conversion to RYGB bypass [20].No other evidence was found in any of the remaining articles.Nonetheless, biliary reflux should be addressed in future studies.
This review verified that technical variations in SASI bypass could induce different rates of weight loss, improvement in comorbidities and complications [28].
These variations included the length of the common limb, which varied between 200 and 350 cm; the size of the gastro-ileal anastomosis, which was 3-4 cm; and the gastroileal anastomosis proximal to the pylorus, which ranged between 3 and 6 cm.
Hosseini et al. demonstrated that a longer biliopancreatic limb was associated with greater improvement in HT, the cause of which is not clear.It may be related to alterations in the levels of ghrelin and GLP-1 hormones with respect to the length of the common limb, but further research is needed to better understand this mechanism [14].
On the other hand, a larger anastomosis size was associated with higher weight loss and a decrease in HT due to food diversion from the gastric pouch to the ileum, leading to an increasement in the malabsorptive effect [14].
Recently, a world consensus meeting was held in India, resulting in a statement suggesting standardization of numerous bariatric surgeries, including SASI bypass.Recommendations to standardise the SASI bypass method included a width of the residual sleeve of 3 cm, the gastric pouch between 150 and 250 cc, separating the gastroileal anastomosis from the pylorus by 2-6 cm, an anastomosis size of 3 cm, and a common limb length of 300 cm [33].
Most studies (14) used the %EWL to evaluate the impact of SASI bypass on the weight of participants [5,6,8,[14][15][16][17][18][19][20][21][22][23]26].The median %EWL at 12 months was 87.14%, which was nearly the same as in the initial report by Mahdy et al. (90%) [5].A wide variation in the values was registered within the studies, varying between 63.9% and 94.33%.This deviation may be attributed to distinct patients' characteristics, or a lack of technical standardization.Studies with a lower %EWL had a higher preoperative BMI.This is consistent with previous studies that showed that patients with a higher BMI had a lower %EWL after bariatric surgery.[31].Comparing these results with a systematic review by Emile et al., which demonstrated that SG had a %EWL of 67.3% after 12 months [28], we can verify that SASI bypass has a better %EWL (87.14%), demonstrating a reasonable weight loss.These results are concordant with those in the comparison of SASI bypass with SG, indicating a clear superiority of SASI bypass.Due to a lack of data, we were unable to compare SASI bypass and OAGB in the meta-analysis.Two studies reported results after two years of follow-up, showing even better results (90.7% [15] and 96.7% [20]).Additionally, one study [15] had a three-year follow-up that had a mean %EWL of 80.6%.
In total, 713 patients were studied for the improvement or remission of T2DM after 12 months in 16 studies.The results ranged between 78.6% and 100%, with a median of 96.35% [5, 6, 8, 9, 14-23, 25, 26], which is higher than the results reported in previous studies for SG, RYGB, and OAGB [28,32].Although there was a wide range of results, only four studies had a rate lower than 90%.These results are concordant with those of our meta-analysis, which demonstrated that patients who underwent SASI bypass had better chances of improvement or resolution than those who underwent SG.Additionally, when compared with the OAGB, the SASI bypass had similar results.
Regarding HT, 15 studies evaluated the rate of complete remission and improvement, in 514 patients after 12 months [5, 8, 9, 14-23, 25, 26].With a median of 75.8%, the findings were between 36.1% and 100%, with only five studies reporting an outcome under 75%.In our analysis, we determined that the SASI bypass had similar results compared to SG and OAGB.
In 11 studies, 340 patients with DL were evaluated after one year to calculate the proportion of full remission and improvement [5, 9, 14-19, 22, 23, 25].The findings ranged from 65 to 100%, with a median of 87.5%, and only one study had a median under 75%.
According to our analysis, SASI bypass had higher chances of DL improvement or resolution than SG but had similar results compared to OAGB.
OSA was evaluated in eight studies that demonstrated an improvement or remission between 20% and 100%, with a median of 89.3% [14,15,[17][18][19][20]22].Although the range of which may cause some variation in results between studies and limits the conclusions presented related to comorbidities.
The high statistical heterogeneity obtained in some of the analyses, can be potentially explained by distinctive patient features, or lack of technical standardization.
Lastly, observational studies, which are more susceptible to bias and confounding variables, constituted nearly all the included studies.Consequently, determining a more effective technique can be more challenging.Therefore, more RCT are required.

Conclusions
SASI bypass has a significant effect on weight loss, and remarkable metabolic control.Additionally, this new technique seems to be a safe bariatric surgical procedure.Nevertheless, there is a need for mid and long-term studies, comparing SASI to other better known and used choices (namely RYGB), in order to ascertain the true clinical advantage of SASI and determine the most robust factors for selecting patients for this procedure.
In conclusion, SASI bypass could be an important tool in the future, but there is a need for studies with longer follow-up periods (> 12 months) to confirm the efficiency and safety of this surgical technique.

Table 1
Studies included in the systematic review and characteristics of patients who underwent SASI bypass